Dear Editor,
In a recent issue of Expert Opinion on Phamacotherapy, an interesting article on the use of statins in the oral treatment of cholesterol gallstones was published Citation[1]. The authors speculated that the therapeutic use of statins in the treatment of cholesterol gallstones could decrease the annual number of cholecystectomies. Some considerations are necessary.
In fact, the effects of statins on gallstones in humans has been controversial Citation[2]. Actually, only in a case-control study the long-term use of statins was associated with a decreased risk of symptomatic gallstone Citation[2], but the dissolution rates in case of multiple cholesterol gallstones are only 40 – 50% after one year of treatment and the recurrence rates after oral bile acid therapy is about 10% per year Citation[2].
Several studies demonstrated that calcium salts (in particular calcium bilirubinate and calcium phosphate) are present in the pigmented center of the 88% of cholesterol gallstones Citation[3]. Calcium ions and mixed mucin glycoproteins, that are secreted by gallbladder mucosa, are also present together in the center of gallstones Citation[4] as showed by ultrastructural studies Citation[5].
The efficacy of oral bile salts and statins in the dissolution of calcium bilirubinate or calcium phosphate, as well as in the elimination of the parietal (gallbladder mucosa) factors of gallstone formation have never been described or proved.
In conclusion, the persistence of the parietal (gallbladder mucosa) factors of cholesterol gallstones heterogeneous nucleation and the persistence of the pigmented center of cholesterol gallstones Citation[5] seems to be the main important conditions related to the failure of oral dissolution therapy of cholesterol gallstones with statin and/or bile acids.
Declaration of interest
The authors state no conflict of interest and have received no payment in preparation of this manuscript.
Bibliography
- Ahmed MH, Hamad MA, Connolly V. Statin as potential treatment for cholesterol gallstones: an attempt to understand the underlying mechanism of action. Expert Opin Pharmacother 2011;12:2673-81
- Di Ciaula A, Wang DQH, Wang HH, Targets for current pharmacological therapy in cholesterol gallstone disease. Gastroenterol Clin North Am 2010;39:245-64
- Kaufman HS, Magnuson TH, Pitt HA, The distribution of calcium salt precipitates in the core, periphery and shell of cholesterol, black pigment and brown pigment gallstones. Hepatology 1994;19:1124-32
- Smith BF, La Mont JT. Identification of gallbladder mucin-bilirubin complex in human cholesterol gallstone matrix. Effects of reducing agents on in vitro dissolution of matrix and intact gallstones. J Clin Invest 1985;76:439-45
- Cariati A, Cetta F, Romano P, Black pigment microstones initially formed within the Rokitansky-Aschoff sinuses of the gallbladder can act as nuclei for the formation of mixed cholesterol stones. Data from scanning electron microscopy analysis of both stones and gallbladder wall. In: Cavallari A, Mazziotti A, Principe A, editors. II World Congress of the International Hepato-Pancreato-Biliary Association. Monduzzi Editore; Bologna: 1996. p. 583-7